• Chimeric antigen receptor T cell (CAR-T) as promising immunotherapy: what do you need to know?
  • Muhammad Sadeqi Nezhad,1,*
    1. Department of Laboratory Science, Young Researchers and Elites Club, Gorgan Branch, Islamic Azad University, Gorgan, Iran


  • Introduction: For many decades human cancer therapies have historically relied on surgery, chemotherapy, and radiotherapy which have demonstrated limited efficacy for patients with late-stage and recurrent gynecological malignancies and often cause substantial and long-lasting adverse effects. In recent years, adaptive therapy with chimeric antigen receptor (CAR) modified T cell, an artificial T cell receptor with supra-physiological properties donating specific capabilities to the T cell, has achieved remarkable response in hematological malignancies, except in solid tumors which remained murky due to some physical and physiological factors. Thus, the primary goal of this review is to make a brief summery about the key features of a typical CAR T cells.
  • Methods: A literature review was conducted for relevant keywords and related articles through prominent databases like Science Direct, ISI Web of Science, Scopus, and PubMed.
  • Results: CAR-modified T cells exhibit a wide variety of remarkable superiority over physiological TCR-containing cells: I. CAR-based cells have the ability to detect cancer cell surface in a human leukocyte antigen (HLA)-independent manner. II. A wide usage of CARs can be summarized in recognizing a variety of antigens, such as glycolipid, carbohydrate and proteins. III. Development of a great number of tumor-specific T cells in a short time makes CAR-T cell therapy a valuable tool towards clinical purposes; while all the mentioned advantages are deprived in physiological TCR. Besides, a typical CAR construction composed of various components including ectodomain, hinge domain, transmembrane domain, costimulatory domain, and endodomain. Each of these components play a key mechanism therefore selecting the most prominent one among diverse proteins can assist the engineered T cells to function properly and effectively. In addition, distance between antigen recognition domains, scFv, and the interest targetable antigen can affect the function of CARs. And a part from the above statements, the modified T cells can be activated and function properly on condition that the impact of affinity, density of receptor and antigen being calculated precisely. In terms of CAR evolution, except the one-fourth generation, engineered T cells experienced different unique types of CAR T cells including off-the-shelf, iCasp9, SUPRA, On/Off switch, and TRUCKs CAR-T cells. Each of these modified T cells exhibit a distinct function and applicability upon the interest targets and malignant cells. Although CAR T cells generation saw a dramatic evolution, still there are some barriers especially in solid tumors that prevent modified T cells to act properly. For example, the presence of immunosuppressive immune cells (MDSCs, suppressive T regulatory, and Th17), dense stromal and myofibroblast surrounding cancer cells, upregulation of inhibitory ligands (PD-L1), and the presence of immunosuppressive cytokines (IL-6, IL-10, TGF-β). Therefore, to overcome the unsolved barriers engineered T cells expressing heparanase, catalase, RIAD, and chemokine receptors were designed to address the hurdles imposed by various malignant cells.
  • Conclusion: The ultimate goal of CAR T-cell therapy is to be curative. A better understanding of the multiples barriers produced new approaches to address the obstacles and enhance tumor eradication by CAR-T cell therapy.
  • Keywords: CAR T cells, engineered T cells, cancer cells, Immunotherapy